Effect of Myrtenol and Its Synergistic Interactions with Antimicrobial Drugs in the Inhibition of Single and Mixed Biofilms of Candida auris and Klebsiella pneumoniae

Maione, Angela; Pietra, Alessandra La; Alteriis, Elisabetta de; Mileo, Aldo; Falco, Maria De; Guida, Marco; Galdiero, Emilia

doi:10.3390/microorganisms10091773

Cited by 16 publications

(25 citation statements)

References 39 publications

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“…For the dual-species biofilm, the suspensions of the two microorganisms were prepared at a final concentration of 10 6 cells mL −1 (ratio 1:1), dispensed (100 μL per well), and incubated. Single- species or dual-species biofilms were stained with crystal violet (CV) solution as described previously [ 17 ]. In brief, biofilms cultured in 96-well plates were air fixed.…”

Section: Methodsmentioning

confidence: 99%

VT-1161—A Tetrazole for Management of Mono- and Dual-Species Biofilms

et al. 2023

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VT-1161 is a novel tetrazole antifungal agent with high specificity for fungal CYP51 (compared to human CYP enzymes) which has been proven to have fewer adverse effects and drug–drug interaction profiles due to fewer off-target inhibitors. In this study, we evaluated the anti-biofilm potential of VT-1161 against mono- and dual-species biofilms of Candida albicans, Klebsiella pneumoniae and Staphylococcus aureus. VT-1161 inhibited planktonic growth of all three strains, with an MIC value of 2 µg mL−1 for C. albicans and 0.5 µg mL−1 for K. pneumoniae and S. aureus, and killed 99.9% of the microbial populations, indicating a cytocidal action. Additionally, VT-1161 showed an excellent anti-biofilm action, since it inhibited mono-microbial biofilms by 80% at 0.5 µg mL−1, and dual-species biofilms of C. albicans/K. pneumoniae and C. albicans/S. aureus by 90% at the same concentration. Additionally, the eradication of mature biofilms after 24 h of VT-1161 exposure was excellent, reaching 90% at 2 μg mL−1 for both mono- and dual-species biofilms. In such mixed biofilms, the use of VT-1161 was revealed to be an alternative treatment because it was able to reduce the number of cells of each species during both inhibition and eradication. Since long-term therapy is necessary for most fungal biofilm infections due to their recurrence and obstinacy, VT-1161 showed low cytotoxicity against normal human cell lines and also against the invertebrate model Caenorhabditis elegans. Considering the excellent anti-biofilm potential and its GRAS (generally recognized as safe) status, VT-1161 may find use in the prevention or therapeutic treatment of mono- or poly-microbial biofilms.

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Section: Methodsmentioning

confidence: 99%

VT-1161—A Tetrazole for Management of Mono- and Dual-Species Biofilms

et al. 2023

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“…The essential oils (EOs) produced by the distillation of aromatic plants are, among the natural substances, the products with the highest antimicrobial potential [ 12 , 13 ]. Several studies have been recently published to evaluate the antifungal activity of EOs against C. auris and its biofilm [ 14 , 15 , 16 , 17 ], and the Cinamomum cassia EO (CC-EO) is one of the most powerful with its bioactive compound cinnamaldehyde [ 18 , 19 ]. C. cassia Presl is a tropical aromatic evergreen tree of the Lauraceae family, commonly used in traditional Chinese medicine.…”

Section: Introductionmentioning

confidence: 99%

Study of the Chemical Profile and Anti-Fungal Activity against Candida auris of Cinnamomum cassia Essential Oil and of Its Nano-Formulations Based on Polycaprolactone

Rosato

Napoli

Granata

et al. 2023

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Background: Candida auris represents an emerging pathogen that results in nosocomial infections and is considered a serious global health problem. The aim of this work was to evaluate the in vitro antifungal efficacy of Cinnamomum cassia essential oil (CC-EO) pure or formulated in polycaprolactone (PCL) nanoparticles against ten clinical strains of C. auris. Methods: nanoparticles of PCL were produced using CC-EO (nano-CC-EO) and cinnamaldehyde (CIN) through the nanoprecipitation method. The chemical profile of both CC-EO and nano-CC-EO was evaluated using SPME sampling followed by GC-MS analysis. Micro-broth dilution tests were performed to evaluate both fungistatic and fungicidal effectiveness of CC-EO and CIN, pure and nano-formulated. Furthermore, checkerboard tests to evaluate the synergistic action of CC-EO or nano-CC-EO with micafungin or fluconazole were conducted. Finally, the biofilm disrupting activity of both formulations was evaluated. Results: GC-MS analysis shows a different composition between CC-EO and nano-CC-EO. Moreover, the microbiological analyses do not show any variation in antifungal effectiveness either towards the planktonic form (MICCC-EO = 0.01 ± 0.01 and MICnano-CC-EO = 0.02 ± 0.01) or the biofilm form. No synergistic activity with the antifungal drugs tested was found. Conclusions: both CC-EO and nano-CC-EO show the same antimicrobial effectiveness and are potential assets in the fight against C. auris.

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“…Essential oils have been shown as both potential antimicrobials and enhancers of conventional antimicrobials [ 27 , 28 ]. In particular, the bicyclic monoterpene myrtenol, a terpene from the myrtenol tree, is able to repress the growth of bacteria [ 37 , 38 ] and fungi [ 36 ] as well as reduce the effective concentrations of some antifungals [ 39 , 40 ]. In our study, the two optical isomers of myrtenol, (−)-myrtenol and (+)-myrtenol, were tested as either antibacterial, antifungal, or enhancers of conventional drugs.…”

Section: Discussionmentioning

confidence: 99%

“…Several chemically synthesized myrtenol derivatives demonstrated significant in vitro antifungal activity against Physalospora piricola with better or comparable antifungal activity than those of positive controls (the commercial fungicides azoxystrobin and chlorothalonil) [ 32 ]. In addition, the combination of myrtenol and antifungal agents reduced the effective concentrations of the latter with synergistic and additive effects [ 39 , 40 ]. The mechanism of myrtenol action is discussible.…”

Section: Introductionmentioning

confidence: 99%

Increasing the Efficacy of Treatment of Staphylococcus aureus–Candida albicans Mixed Infections with Myrtenol

et al. 2022

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Infectious diseases caused by various nosocomial microorganisms affect worldwide both immunocompromised and relatively healthy persons. Bacteria and fungi have different tools to evade antimicrobials, such as hydrolysis damaging the drug, efflux systems, and the formation of biofilm that significantly complicates the treatment of the infection. Here, we show that myrtenol potentiates the antimicrobial and biofilm-preventing activity of conventional drugs against S. aureus and C. albicans mono- and dual-species cultures. In our study, the two optical isomers, (-)-myrtenol and (+)-myrtenol, have been tested as either antibacterials, antifungals, or enhancers of conventional drugs. (+)-Myrtenol demonstrated a synergistic effect with amikacin, fluconazole, and benzalkonium chloride on 64–81% of the clinical isolates of S. aureus and C. albicans, including MRSA and fluconazole-resistant fungi, while (-)-myrtenol increased the properties of amikacin and fluconazole to repress biofilm formation in half of the S. aureus and C. albicans isolates. Furthermore, myrtenol was able to potentiate benzalkonium chloride up to sixteen-fold against planktonic cells in an S. aureus–C. albicans mixed culture and repressed the adhesion of S. aureus. The mechanism of both (-)-myrtenol and (+)-myrtenol synergy with conventional drugs was apparently driven by membrane damage since the treatment with both terpenes led to a significant drop in membrane potential similar to the action of benzalkonium chloride. Thus, due to the low toxicity of myrtenol, it seems to be a promising agent to increase the efficiency of the treatment of infections caused by bacteria and be fungi of the genus Candida as well as mixed fungal–bacterial infections, including resistant strains.

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Effect of Myrtenol and Its Synergistic Interactions with Antimicrobial Drugs in the Inhibition of Single and Mixed Biofilms of Candida auris and Klebsiella pneumoniae

Cited by 16 publications

References 39 publications

VT-1161—A Tetrazole for Management of Mono- and Dual-Species Biofilms

VT-1161—A Tetrazole for Management of Mono- and Dual-Species Biofilms

Study of the Chemical Profile and Anti-Fungal Activity against Candida auris of Cinnamomum cassia Essential Oil and of Its Nano-Formulations Based on Polycaprolactone

Increasing the Efficacy of Treatment of Staphylococcus aureus–Candida albicans Mixed Infections with Myrtenol

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